miR-375 Levels Research Articles

Increased oxygen stimulation promotes chemoresistance and phenotype shifting through PLCB1 in gliomas

Gliomas, the most common CNS (central nerve system) tumors, face poor survival due to severe chemoresistance exacerbated by hypoxia. However, studies on whether altered hypoxic conditions benefit for chemo-sensitivity and how gliomas react to increased oxygen stimulation are limited. In this study, we demonstrated that increased oxygen stimulation promotes glioma growth and chemoresistance. Mechanically, increased oxygen stimulation upregulates miR-1290 levels. miR-1290, in turn, downregulates PLCB1, while PLCB1 facilitates the proteasomal degradation of β-catenin and active-β-catenin by increasing the proportion of ubiquitinated β-catenin in a destruction complex-independent mechanism. This process inhibits PLCB1 expression, leads to the accumulation of active-β-catenin, boosting Wnt signaling through an independent mechanism and ultimately promoting chemoresistance in glioma cells. Pharmacological inhibition of Wnt by WNT974 could partially inhibit glioma volume growth and prolong the shortened survival caused by increased oxygen stimulation in a glioma-bearing mouse model. Moreover, PLCB1, a key molecule regulated by increased oxygen stimulation, shows promising predictive power in survival analysis and has great potential to be a biomarker for grading and prognosis in glioma patients. These results provide preliminary insights into clinical scenarios associated with altered hypoxic conditions in gliomas, and introduce a novel perspective on the role of the hypoxic microenvironment in glioma progression. Furthermore, the outcomes reveal the potential risks of utilizing hyperbaric oxygen treatment (HBOT) in glioma patients, particularly when considering HBOT as a standalone option to ameliorate neuro-dysfunctions or when combining HBOT with a single chemotherapy agent without radiotherapy.

MiR-1290 induces endothelial-to-mesenchymal transition and promotes vascular restenosis after angioplasty by targeting FGF2

Background and aimsEndothelial-to-mesenchymal transition (EndMT) is an important reason for restenosis but the underlying mechanisms need to be further explored. Therefore, the purpose of this study is to screen significantly different microRNAs (miRNAs) and assess their functions and downstream pathways. MethodsThis study screened several miRNAs with significant differences between human arterial segments from restenosis patients and healthy volunteers using whole transcriptome resequencing and real-time quantitative reverse transcription PCR (qRT-PCR). We explored the correlation between miR-1290 and EndMT using Western blot, qRT-PCR, Pearson correlation analysis and further functional gain and loss experiments. Subsequently, we identified the direct downstream target of miR-1290 by bioinformatics analysis, RNA pull-down, double Luciferase reporter gene and other functional experiments. Finally, rat carotid artery balloon injury model demonstrated the therapeutic potential of miR-1290 regulator. ResultsWe screened 129 differentially expressed miRNAs. Among them, miR-1290 levels were significantly higher in restenosis arteries than in healthy arteries, and as expected, EndMT was functionally enhanced with miR-1290 overexpression and comparatively weakened when miR-1290 was knocked down. In addition, fibroblast growth factor-2 (FGF2) was established as the downstream target of miR-1290. Finally, we utilized an animal model and found that low miR-1290 levels could alleviate EndMT and the progression of restenosis. ConclusionsOur study demonstrated the strong regulatory effects of miR-1290 on EndMT, endometrial hyperplasia and restenosis, which could be useful as biomarker and therapeutic target for stent implantation in patients with arterial occlusive disease of the lower extremities.

Association between expression level of the miR-320, miR-182, miR-223 and miR-486 and body composition among young Polish female volleyball players

The expression of circulating microRNAs appears to be a promising indicator of physical strength. The objective of this study was to determine whether there is an association between the expression level of four selected microRNAs and body composition over time among young female volleyball players. Blood samples and body composition measurements were taken from 7 females who are Polish volleyball players before and after 5 matches played out between the years 2017 and 2018. The blood spots were used to assess the expression of four microRNAs: miR-320, miR-182, miR-223, and miR-486. Fat mass, PFB% and BMI were positively correlated with expression level (exp.l) of miR-182. The miR-320 the exp.l was positively correlated with muscle mass and TBW. There were inverse correlations between miR-486 exp.l and PBF%, as well as between miR-486 exp.l and body mass, muscle mass, TBW, FFM, and BMR. Conversely, there were positive correlations between miR-486 exp.l and body mass and fat mass. The miR-182 may be positively correlated with fat tissue, miR-320 was positively correlated with muscle mass, and miR-486 was negatively correlated with fat mass. Overall, our study shows that the expression of miR-182, miR-320, and miR-486 is associated with body composition. The results of our study also suggest that exercise may decrease the level of miR-486. The authors are grateful for the support of the Laboratory of Microscopic Imaging and Specialized Biological Techniques of the University of Lodz.

Effect of microRNA-141-3p, E2F3, CDK3, and KAT2B overexpression on histologic tumor grade and metastasis status in untreated breast cancer tissues

Introduction: Increasing evidence has reported gene expression alterations in breast cancer (BC) tissues, necessitating their investigating to highlight the molecular basis of the disease development or progression. This study investigated the expression of miR-141, E2F3, CDK3, TP53, and KAT2B, and their association with histologic grade and metastasis in BC tissues. Methods: The RNA expression level of miR-141, E2F3, CDK3, TP53, and KAT2B genes was analyzed in 23 BC and 23 normal tissue samples by RT-qPCR. The associations of the expression level of these genes with clinicopathological features of the BC tissue samples were evaluated. The study also explored the correlation between RNA levels of genes and miR-141. Results: Expression of miR-141, E2F3, CDK3, and KAT2B demonstrated significantly higher levels in BC tumor than normal tissues. TP53 expression showed an increase in tumor compared to normal tissues, although it was insignificant. Moreover, increased RNA expression of miR-141, E2F3, CDK3, and KAT2B corresponded to the advanced stage and regional metastasis of BC. Additionally, the results demonstrated a significant correlation between RNA expression levels of miR-141 with CDK3 and E2F3 with KAT2B. Conclusion: Our findings highlighted clinicopathologic indicators that were relevant to aggressive BC. Besides, Correlations between overexpression of miR-141, E2F3, CDK3, and KAT2B in BC tissues suggest regulatory effects. Taken together, it seems results of this study could provide evidence that dysregulation of gene expression contributes significantly to unveiling the underlying molecular basis of BC.

MicroRNA-141-regulated KLK10 and TNFSF-15 gene expression in hepatoblastoma cells as a novel mechanism in liver carcinogenesis

Liver cancer is one of the most pivotal global health problems, leading hepatocellular carcinoma (HCC) with a significant increase in cases worldwide. The role of non-coding-RNA in cancer proliferation and carcinogenesis has attracted much attention in the last decade; however, microRNAs (miRNAs), as non-coding RNA, are considered master mediators in various cancer progressions. Yet the role of miR-141 as a modulator for specific cellular processes in liver cancer cell proliferation is still unclear. This study identified the role of miR-141 and its potential functions in liver carcinogenesis. The level of miR-141 in HepG2 and HuH7 cells was assessed using quantitative real-time PCR (qRT-PCR) and compared with its expression in normal hepatocytes. A new miR-141 construct has been performed in a CMV promoter vector tagged with GFP. Using microarray analysis, we identified the potentially regulated genes by miR-141 in transfected HepG2 cells. The protein profile of the kallikrein-related peptidase 10 (KLK10) and tumor necrosis factor TNFSF-15 was investigated in HepG2 cells transfected with either an inhibitor, antagonist miR-141, or miR-141 overexpression vector using immunoblotting and flow cytometry assay. Finally, ELISA assay has been used to monitor the produced inflammatory cytokines from transfected HepG2 cells. Our findings showed that the expression of miR-141 significantly increased in HepG2 and HuH7 cells compared to the normal hepatocytes. Transfection of HepG2 cells with an inhibitor, antagonist miR-141, showed a significant reduction of HepG2 cell viability, unlike the transfection of miR-141 overexpression vector. The microarray data of HepG2 cells overexpressed miR-141 provided a hundred downregulated genes, including KLK10 and TNFSF-15. Furthermore, the expression profile of KLK10 and TNFSF-15 markedly depleted in HepG2 cells transfected with miR-141 overexpression accompanied by a decreasing level of interleukin 6 (IL-6) and tumor necrosis factor-alpha (TNF-α), indicating the role of miR-141 in HepG2 cell proliferation and programmed cell death. Interestingly, the experimental rats with liver cancer induced by Diethylnitrosamine injection further confirmed the upregulation of miR-141 level, IL-10, and TNF-α and the disturbance in KLK10 and TNFSF-15 gene expression compared with their expression in normal rats. The in-silico online tools, IntaRNA and miRWalk were used to confirm the direct interaction and potential binding sites between miR-141 and identified genes. Thus, the seeding regions of potential targeted sequences was cloned upstream of luciferase reporter gene in pGL3 control vector. Interestingly, the luciferase activities of constructed vectors were significantly decreased in HepG2 cells pre-transfected with miR-141 overexpression vector, while increasing in cells pre-transfected with miR-141 specific inhibitor. In summary, these data suggest the crucial role of miR-141 in liver cancer development via targeting KLK10 and TNFSF-15 and provide miR-141 as an attractive candidate in liver cancer treatment and protection.

M6A Methylation Mediates the Function of the circRNA-08436/miR-195/ELOVL6 Axis in Regards to Lipid Metabolism in Dairy Goat Mammary Glands.

The nutritional value of goat milk is determined by the composition of its fatty acids, with particular importance placed on the role of unsaturated fatty acids in promoting human health. CircRNAs have been known to affect fatty acid metabolism through different pathways. In this study, high-throughput sequencing was employed to construct expression profiles of mammary tissue harvested during the dry period and peak lactation stages of dairy goats. Differentially expressed circRNAs and mRNAs were screened, revealing significantly higher expression levels of circRNA-08436 and ELOVL6 during the peak lactation period compared with the dry period. Thus, circRNA-08436 and ELOVL6 were chosen for subsequent studies. The findings demonstrated that circRNA-08436 not only promotes the synthesis of triglyceride (TAG) and cholesterol in goat mammary epithelial cells (GMECs), but also increases the concentrations of saturated fatty acids in the cells. Through the utilization of software prediction, the dual luciferase reporter system, and qRT-PCR, it was observed that circRNA-08436 binds to miR-195, with its overexpression reducing the expression levels of miR-195 and inhibiting TAG synthesis. In addition, circRNA-08436 upregulated the expression levels of the miR-195 target gene ELOVL6. The data also revealed that YTHDC1 facilitated the transport of circRNA-08436 from the nucleus to the cytoplasm, while YTHDC2 in the cytoplasm functioned as a "reader" to identify and degrade circRNA-08436. Taken together, these findings contribute to a better understanding of the molecular regulation of fatty acid metabolism in the mammary glands of dairy goats, thus offering a sound theoretical basis for the production of high-quality goat milk.

Expression Levels and Clinical Values of miR-195, miR-424, miR-10b, miR-103a-3p, and miR-542-3p in Vasculo-Behçet's Disease.

MicroRNAs (miRNAs) are involved in a range of pathological and biological processes. Vascular involvement is an important complication associated with morbidity and mortality in Behçet's disease (BD). In this study, we aimed to evaluate the expression levels of miR-195, miR-424, miR-10b, miR-103a-3p, and miR-542-3p in Turkish patients with BD, and their possible association with vascular involvement and clinical activity. This cross-sectional study included 61 BD patients and 25 age- and sex-matched healthy individuals. The patients were categorised into two groups based on the presence or absence of vascular involvement. Demographic data, disease duration, disease activity, and medical treatments were recorded. Disease activity was evaluated using the Behçet's Disease Current Activity Form (BDCAF) and the Behçet's Syndrome Activity Scale (BSAS). The expression levels of miRNAs were measured using real-time quantitative polymerase chain reaction (RT-qPCR). The comparison of the clinical features of BD patients with and without vascular involvement revealed no significant difference. However, the expression levels of miR-195, miR-424, miR-10b, miR-103a-3p, and miR-542-3p were significantly higher in BD patients than in healthy controls (p<0.001, p<0.001, p=0.010, p<0.01, p=0.039, respectively). Moreover, the expression level of miR-195 was significantly higher in vasculo-Behçet patients than in the other groups (p=0.0318). However, no significant association was found between the expression levels of miR-195 and clinical activity. Our study results indicated elevated serum levels of miR-195 in BD patients, which may be associated with vascular involvement. Therefore, miR-195 could potentially serve as a biomarker for the diagnosis and monitoring of vasculo-Behçet's disease.

Influence of Fragmented Human DNA on the Relationship between MicroRNA (miR-21, -221, -222, and -429) of the Lymph and the Structure of the Thymus after Surgical Treatment and Chemotherapy for Breast Cancer.

In female Wistar rats, we studied the relationship between the levels of miR-21, miR-221, miR-222, and miR-429 in the lymph and morphometric parameters of the thymus after surgical treatment of breast cancer, chemotherapy, and administration of fragmented human DNA. The levels of pro-oncogenic miR-221 and miR-222 in the lymph decreased after surgical treatment and chemotherapy in comparison with the pathological controls. Positive correlations of miR-221 and miR-429 with small lymphocytes in the cortical substance and miR-21 and miR-429 with small lymphocytes of the medullary substance of the thymus were revealed. After administration of fragmented human DNA, an increase in the level of miR-429 in the lymph was detected in comparison with resection+chemotherapy. In the subcapsular zone of the cortical substance, proliferative activity and the number of cells with pyknotic nuclei decreased. The number of macrophages increased in all structural zones of the thymus. The following interrelations were revealed: in the subcapsular zone of the cortical substance, correlations of immunoblasts with miR-222, macrophages and mitotically dividing cells with miR-429; in the central part of the cortical substance and medullary substance, as well as the cortical-medullary zone, correlation of miR-221 with mitotically dividing cells; in the central part of the medullary substance, correlation of miR-429 with epithelial cells.

Expression of MiR-144/451 in Different Types of Anemia

To investigate the expression level and clinical correlation of microRNA-144/451 gene cluster (miR-144/451) in different types of anemia. The peripheral blood of patients with aplastic anemia (AA), myelodysplastic syndrome (MDS) and diffuse large B-cell lymphoma (DLBCL) who had been diagnosed with anemia for the first time and after chemotherapy were collected. The expression levels of miR-144 and miR-451 were measured by RT-qPCR, and the correlation between the expression levels of miR-144 and miR-451 and routine laboratory indexes was analyzed by Spearman correlation analysis. The expression levels of miR-144 and miR-451 in the peripheral blood of AA and MDS patients were significantly lower than those in normal controls (all P < 0.01). No statistical differences were observed in the expression level of miR-144 in three subgroups of DLBCL patients (P >0.05), while the expression level of miR-451 in peripheral blood of three subgroups of DLBCL patients were significantly higher than those in normal controls (all P < 0.05). Correlation analysis showed that the expression levels of miR-144 and miR-451 in AA patients were positively correlated with red blood cell distribution width-coefficient of variation (RDW-CV) (r =0.629, 0.574). There were no significant correlations between the expression levels of miR-144 and miR-451 and laboratory parameters in MDS and DLBCL patients. Different types of anemia disorders have varying levels of miR-144 and miR-451 expression, which is anticipated to develop into a secondary diagnostic and differential diagnostic indicator for clinical anemia diseases.

Hyperoxia-Induced miR-195 Causes Bronchopulmonary Dysplasia in Neonatal Mice.

Background: Exposure to hyperoxia is an important factor in the development of bronchopulmonary dysplasia (BPD) in preterm newborns. MicroRNAs (miRs) have been implicated in the pathogenesis of BPD and provide a potential therapeutic target. Methods: This study was conducted utilizing a postnatal animal model of experimental hyperoxia-induced murine BPD to investigate the expression and function of miR-195 as well as its molecular signaling targets within developing mouse lung tissue. Results: miR-195 expression levels increased in response to hyperoxia in male and female lungs, with the most significant elevation occurring in 40% O2 (mild) and 60% O2 (moderate) BPD. The inhibition of miR-195 improved pulmonary morphology in the hyperoxia-induced BPD model in male and female mice with females showing more resistance to injury and better recovery of alveolar chord length, septal thickness, and radial alveolar count. Additionally, we reveal miR-195-dependent signaling pathways involved in BPD and identify PH domain leucine-rich repeat protein phosphatase 2 (PHLPP2) as a novel specific target protein of miR-195. Conclusions: Our data demonstrate that high levels of miR-195 in neonatal lungs cause the exacerbation of hyperoxia-induced experimental BPD while its inhibition results in amelioration. This finding suggests a therapeutic potential of miR-195 inhibition in preventing BPD.

#2229 miR-186, a potential noninvasive diagnostic biomarker of Membranous nephropathy in urinary microparticles

Abstract Background and Aims Membranous nephropathy (MN) is one of the most common causes of nephrotic syndrome, and is associated with podocyte damage and proteinuria. Invasive biopsy is the gold-standard diagnostic method for this disease. The use of specific biomarkers, such as microparticles (MPs) originating from damaged podocytes released in a patient's urine, has been proposed as an early, noninvasive, and repetitive diagnostic method. According to the previous studies, MPs derived from podocytes are present in the urine of patients with different glomerulonephritis, such as diabetic nephropathy, lupus nephritis, renal injury in preeclampsia, and renovascular hypertensive disorders. The analysis of urinary microparticle-derived miRNAs from patients with kidney diseases can help detect diagnostic biomarkers. This study aimed to analyze podocyte damage-related miRNAs in MN, miR-30c, miR-135, and miR-18 in the urinary MP of MN patients to identify appropriate candidate biomarkers for MN Method Urine samples from 30 patients with membranous nephropathy and 16 healthy individuals were collected to extract podocyte MPs using ultracentrifugation. Characterization of these particles was determined using the specific protein marker of MPs, TSG-101, and the podocyte-specific marker Nephrin, by western blotting, and SEM was used to check the size and morphology. The expression levels of microRNAs extracted from podocyte MPs, miR-30c, miR-135, and miR-186, were also evaluated by real-time PCR. Results The evaluation of the characteristics of MPs showed that there were many particles with a size of more than 100 nm in the urine sample, and there were higher levels of the specific markers TSG-101 and Nephrin in the urine samples of MGN patients than in the control samples (P &amp;lt; 0.001). The expression level of miR-186 was compared between the three studied groups and based on the results of the expression of this miRNA in the group of membranous nephropathy patients compared to healthy people group, there was a significant increase in expression (P = 0.000) Conclusion This study showed that although the expression levels of miR-186 in podocyte MPs samples extracted from the urine of patients with MN were significantly changed compared to the studied controls, more studies should be performed to determine the diagnostic values.

The Genetic Variants of Long Noncoding RNA MEG3 and Its Association to the Clinical Features of Diabetic Retinopathy

Purpose This study aimed to investigate the potential correlation between the single-nucleotide polymorphism (SNP) of maternally expressed gene 3 (MEG3) and the clinical manifestations of diabetic retinopathy (DR). Methods Five loci of MEG3 SNPs including rs4081134 (G/A), rs10144253 (T/C), rs7158663 (G/A), rs3087918 (T/G) and rs11160608 (A/C) were genotyped by TaqMan allelic discrimination in 457 non-DR patients and 280 DR individuals. Results The distribution frequency of MEG3 SNP rs7158663 GA (AOR: 0.683, 95% CI: 0.478-0.975, p = 0.036) and MEG3 SNP rs7158663 GA + AA (AOR: 0.686, 95% CI: 0.487-0.968, p = 0.032) were significantly lower in the DR group. And the MEG3 SNP rs7158663 GA + AA (AOR: 0.610, 95% CI: 0.377-0.985, p = 0.043) demonstrated a significantly lower distribution frequency in the male DR group. Besides, the DR patients with MEG3 SNP rs7158663 GA + AA genotype showed a significantly lower HbA1c level than the DR patients with MEG3 SNP rs7158663 GG genotype (7.29 ± 1.23 versus 7.74 ± 1.49, p = 0.013). Moreover, in the analysis using data from gene expression data series database, a higher MEG3 level was significantly correlated to a lower miR-182 level in the database (p = 0.0114). Conclusions In this study, the distribution frequency of MEG3 SNP rs7158663 GA + AA genotype was lower in DR, while the DR would develop under lower HbA1c level in DM patients with this MEG3 SNP variant.

Logic Signal Amplification System for Sensitive Electrochemiluminescence Detection and Subtype Identification of Cancer Cells.

Achieving sensitive detection and accurate identification of cancer cells is vital for diagnosing and treating the disease. Here, we developed a logic signal amplification system using DNA tetrahedron-mediated three-dimensional (3D) DNA nanonetworks for sensitive electrochemiluminescence (ECL) detection and subtype identification of cancer cells. Specially designed hairpins were integrated into DNA tetrahedral nanostructures (DTNs) to perform a catalytic hairpin assembly (CHA) reaction in the presence of target microRNA, forming hyperbranched 3D nanonetworks. Benefiting from the "spatial confinement effect," the DNA tetrahedron-mediated catalytic hairpin assembly (DTCHA) reaction displayed significantly faster kinetics and greater cycle conversion efficiency than traditional CHA. The resulting 3D nanonetworks could load a large amount of Ru(phen)32+, significantly enhancing its ECL signal, and exhibit detection limits for both miR-21 and miR-141 at the femtomolar level. The biosensor based on modular logic gates facilitated the distinction and quantification of cancer cells and normal cells based on miR-21 levels, combined with miR-141 levels, to further identify different subtypes of breast cancer cells. Overall, this study provides potential applications in miRNA-related clinical diagnostics.

Evaluation of miR-130b-3p and miR-375 levels and telomere length with telomerase activity in prostate cancer

Prostate cancer (PC) is the most frequent cancer in males, as well as the second highest cause of cancer-related deaths in men. Differences in expression levels of miRNAs were linked with prostat cancer pathogenesis. qPCR was used to evaluate the expression of miR-130b-3p and miR-375 in Benign Prostate Hyperplasia (BPH (n = 20) and PC (n = 22, pre- and post-operative) patients plasma. Relative telomere lengths (RLTs) in genomic DNA isolated from plasma were measured with qPCR, and telomerase activity analyzed by the ELISA method. PSA levels of PC patients were greater than of BPH patients (p = 0.0473). miR-130b-3p and miR-375 levels were significantly lower in pre-operative specimens of PC patients according to BPH (p = 0,0362, p = 0.0168, respectively). Similarly, post-operative miR-375 levels were lower in PC patients than in BPH patients (p = 0.1866). BPH patients had shorter RTLs than PC patients in both pre- (p=0.0438) and post-operative (p=0.0297) specimens. Telomerase activity was higher in PC patients than BPH(p = 0.0129). Interestingly, telomerase activity was further increased after surgery (p = 0.0003). We aim to identify the levels of miR-130b-3p and miR-375 expression and their relationship with telomerase activity in PC patients. Our data suggest that miRNAs and telomere length (TL) with telomerase activity may play a role in regulating prostate tumorgenesis and may be used as biomarkers for PC diagnosis.

Identification and analysis of genes associated with the severity and prognosis of sepsis.

With rapid progression, severe illness and high fatality rate, sepsis has become an acute and critical condition that seriously threatens human life and health. To detect miR-210 and miR-494 expression in patients with sepsis and their relationship with severity and prognosis. A total of 165 sepsis patients participated, including 105 patients with septic non-shock and 60 patients with septic shock. 53 sepsis patients died in 28 days, and 112 patients survived. The clinical information of all sepsis patients was retrospectively searched and reviewed. Based on the status of 28-day survival, they were categorized into survival group and death group. The expression levels in each group were compared on the first, third and seventh day. The ROC curve was applied to know the expression level of plasma miR-210 and miR-494 to predict the death. The two miRNAs expression of the septic shock group were significantly higher than that in sepsis non-shock group on the first, third and seventh day (all were P< 0.05). The ROC curve found that the AUC combined to predict the death on the third day was the largest, which was 0.925 (95%CI: 0.864-0.983). The sensitivity and specificity were 94.6% and 86.3%, respectively. The increased expression levels of plasma miR-210 and miR-494 are closely relevant to the severity and prognosis of sepsis patients. Combining the two items on the third day can predict the death of sepsis patients.

The interrelation between the high expression level of MIR34a and the trisomic abortion materials.

The underlying mechanism and constitution of spontaneous abortions are complicated and heterogeneous. Many factors, including epigenetic scenarios like micro-ribonucleic acids (miRNAs, MIRs), can additively affect the progression of pregnancy losses. This study aimed to evaluate whether the expression levels of placental inhibitor and/or activator miRNAs had a difference between the numerically abnormal and normal karyotyped spontaneous abortions. The case-control study included 100 spontaneous abortion materials consisting of trophoblastic tissues with 42 disomies (controls), 43 aneuploidies (including trisomy 16, 21, 22, and monosomy X), and 15 triploidies. Disomic abortion materials with XX normal karyotypes were omitted from the study to exclude possible maternal decidual cell contamination. Total RNA isolation was performed with TRIzol™ reagent directly from frozen trophoblastic tissues, and the mature miRNAs were obtained by reverse transcription via quantitative real-time polymerase chain reaction (qRT-PCR). Then, the expression levels of placental activators MIR378a-5p, MIR376c, MIR195, and inhibitors MIR34a and MIR210 were relatively evaluated using MIR130 as a reference. The expression level of placental inhibitor MIR34a was detected to be high in trisomic abortion materials (trisomy 16 and 21) when compared to the disomic ones (p = 0.0324). MIR195 (p = 0.0484) and MIR34a (p = 0.0346) expression levels were increased in numerically abnormal cases with advanced maternal age compared to the disomic ones within all maternal ages. It seems likely that the high expression level of MIR34a and the coexistence of trisomic abortion materials are quite interrelated with the additive effect of advanced maternal age.

Role of microRNAs in cognitive decline related to COVID‑19 (Review).

The likelihood and severity of cognitive decline related to coronavirus disease 2019 (COVID-19) have been shown to be reflected by the severity of the infection and concomitant alterations in specific biomarkers. The present review discusses the role of microRNAs (miRNAs/miRs) as biomarkers in COVID-19 and the potential molecular mechanisms of cognitive dysfunction related to COVID-19. A systematic search of published articles was carried out from January 31, 2000 to December 31, 2022 using the PubMed, ProQuest, Science Direct and Google Scholar databases, combining the following terms: 'COVID-19' OR 'SARS-CoV-2' OR 'post-COVID-19 effects' OR 'cognitive decline' OR 'neurodegeneration' OR 'microRNAs'. The quality of the evidence was evaluated as high, moderate, low, or very low based on the GRADE rating. A total of 36 studies were identified which demonstrated reduced blood levels of miR-146a, miR-155, Let-7b, miR 31 and miR-21 in patients with COVID-19 in comparison with a healthy group. The overexpression of the Let-7b may result in the downregulation of BCL-2 during COVID-9 by adjusting the immune responses between chronic inflammatory disease, type 2 diabetes, COVID-19 and cognitive impairment. The reduced expression of miR-31 is associated with cognitive dysfunction and increased microcoagulability in patients with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). miR-155 mediates synaptic dysfunction and the dysregulation of neurotransmitters due to acute inflammation, leading to brain atrophy and a subcortical cognitive profile. The downregulation of miR-21 in patients with COVID-19 aggravates systemic inflammation, mediating an uncontrollable immune response and the failure of T-cell function, provoking cognitive impairment in patients with SARS-CoV-2. On the whole, the present review indicates that dysregulated levels of miR-146a, miR-155, Let-7b, miR-31, and miR-21 in the blood of individuals with COVID-19 are associated with cognitive decline, the chronic activation of immune mechanisms, the cytokine storm, and the vicious cycle of damage and systemic inflammation.

Sodium tanshinone IIA sulfonate inhibits tumor growth via miR-138 upregulation in intermittent hypoxia-induced xenograft mice.

We studied the functions of sodium tanshinone IIA sulfonate (TSA) in inducing tumor growth in obstructive sleep apnea (OSA)-mimicking intermittent hypoxia (IH) xenograft mice and the underlying potential molecular mechanism. RNA sequencing was conducted to screen the differentially expressed microRNAs in cell lines exposed to IH with or without TSA treatment. As part of the 5-week in vivo study, we treated xenograft mice with 8-h IH once daily. TSA and miR-138 inhibitors or mimics were administrated appropriately. In addition, we performed real-time quantitative polymerase chain reaction (RT-PCR), Western blotting, enzyme-linked immunosorbent assay (ELISA), immunohistochemistry (IHC), microvessel density (MVD), and terminal deoxynucleotidyl transferase dUTP nick-end labeling (TUNEL) assays. RNA sequencing and RT-PCR results demonstrated that TSA increased the levels of miR-138 under IH conditions in vitro. TSA reduced the IH-stimulated high levels of hypoxia-induced factor-1α and vascular endothelial growth factor. Furthermore, IH contributed to high tumor migration, invasion, MVD, and low apoptosis. TSA attenuated IH-mediated tumor proliferation, migration, invasion, MVD, and increased apoptosis, whereas miR-138 inhibitor interrupted the effect of TSA on treating IH-induced tumor behaviors. OSA mimicking IH facilitates tumor growth and reduces miR-138 levels. TSA inhibits IH-induced tumor growth by upregulating the expression of miR-138.

EXPRESSION PROFILE OF miR-145, -182, -21, -27a, -29b, and -34a IN BREAST CANCER PATIENTS OF YOUNG AGE.

Breast cancer (BC) in young women remains a significant public health concern. While progress has been made in understanding the etiology, diagnosis, and treatment of BC in this population, challenges persist. The identification and utilization of prognostic biomarkers offer valuable tools for tailoring treatment strategies and improving outcomes for BC patients. To evaluate the relationship between the expression of tumor-associated microRNAs and the clinical and pathological features of BC in young patients. The work is based on the results of the examination and treatment of 50 women younger than 45 years with stage I-II BC. miR-145, -182, -21, -27a, -29b, and -34a expression in tumor samples was analyzed by the real-time reverse transcription polymerase chain reaction. Higher expression of miR-182, -21, and -29b and lower levels of miR-27a were associated with tumor stage in young BC patients. Patients without lymph node metastases (N0) had significantly higher levels of miR-182, -27a, and -34a and lower levels of miR-29b compared to N1 cases (p < 0.05). Expression of miR-145, -182, -21, -27a, and -29b was associated with molecular BC subtypes. Obtained results show that a high malignancy degree of BC in young women is associated with an increase in the miR-182, -21, -29b, and -34a expressions and a decrease in the miR-27a level in the tumor tissue, which indicates the prospects of the use of them for predicting the aggressiveness of the disease.

Association of ATG10 rs1864183, ATG16L1 rs2241880 and miR-126 with esophageal cancer.

In India, esophageal cancer (EC) is among the major cause of cancer-related deaths in both sexes. In recent past, autophagy has emerged as one of the crucial process associated with cancer. In the development of EC, the role of autophagy and the precise molecular mechanism involved has yet to be fully understood. Recently, a small number of studies have proposed how variations in autophagy genes affect the growth and development of EC. Micro-RNA's are also known to play a critical role in the development of EC. Here, we examined the relationship between the risk of EC and two single-nucleotide polymorphisms (SNPs) in the key autophagy genes, ATG10 rs1864183 and ATG16L1 rs2241880. We also analyzed the association of miR-107 and miR-126 with EC as these miRNA's are associated with autophagy. A total of 230 EC patients and 230 healthy controls from North-west Indian population were enrolled. ATG10 rs1864183 and ATG16L1 rs2241880 polymorphism were analyzed using TaqMan genotyping assay. Expression levels of miR-107 and miR-126 were analyzed through quantitative PCR using SYBR green chemistry. We found significant association of CT + CC genotype (OR 0.64, p = 0.022) in recessive model for ATG10 rs1864183 polymorphism with decreased EC risk. For ATG16L1 rs2241880 polymorphism significant association for AG genotype (OR 1.48, p = 0.05) and G allele (OR 1.43, p = 0.025) was observed for increased EC risk. Expression levels of miR-126 were also found to be significantly up regulated (p = 0.008). Our results suggest that ATG10 rs1864183, ATG16L1 rs2241880 and miR-126 may be associated with esophageal carcinogenesis and warrant further investigation.